Probiotics

Probiotics are defined as nonpathogenic microorganisms that, when administered in adequate amounts, can offer health benefits to a host and have proven to be capable of preventing or improving some diseases. These combinations of live beneficial bacteria, sometimes with yeasts included, naturally live in a person's body. These bacteria are part of the body's microbiome and work to keep the body healthy. Microbiomes are combinations of bacteria, fungi, viruses, and protozoa. Each person's microbiome is unique, even between twins.

For a microbe to be considered probiotic, it must have the following characteristics:

• Be isolated from a human
• Survive in an intestinal tract after ingestion
• Have a proven benefit for human health
• Can be safely consumed

At their simplest, these good bacteria work to keep bad bacteria in check and maintain balance within a body. The common types of probiotic bacteria include Lactobacillus and Bifidobacterium, while the most common type of yeast found in probiotics is saccharomyces boulardii. These bacteria also work to support immune functions and control inflammation. The functions of the bacteria also include:

• Aiding with digestion
• Supporting immune functions
• Creating vitamins
• Helping support cells that line the gut to prevent bad bacteria that has been consumed from entering the blood
• Helping break down and absorb medications

There is a collection of research around the benefits of increasing probiotics in the body for various health and medical conditions, either through food or supplementation. In the case of supplementation, probiotics can be combined with prebiotics, which are complex carbohydrates that feed the microorganisms in a person's gut and keep those microorganisms healthy. These prebiotics can include inulin, pectin, and resistant starches. Foods high in available probiotics include:

• Yogurt
• Buttermilk
• Sourdough bread
• Cottage cheese
• Kombucha
• Tempeh
• Fermented pickles
• Fermented sauerkraut
• Kimchi
• Miso soup

Digestive disease specialists have recommended probiotic supplements for disorders that frustrate conventional medicine. Further clinical studies have suggested that probiotic therapy can help treat several gastrointestinal ills, delay the development of allergies in children, and prevent or treat vaginal and urinary infections in women. The beneficial effects of probiotics related to the intestinal tract differ from one individual to another due to a difference of intestinal microbiota. This is because probiotics, in general, should compete with indigenous bacteria for nutrients and a niche in the intestine, but they may also establish a symbiotic relationship with certain indigenous bacteria. Thus, the difference in indigenous intestinal microbiota has significant influence on the magnitude of the probiotic effects.

The best case for probiotic use or probiotic therapy has been in the treatment of diarrhea. Controlled trials have shown that probiotics can shorten the course of infectious diarrhea in infants and children, although not in adults. Other studies have found that probiotics can reduce antibiotic-associated diarrhea by 60 percent when compared with a placebo. Further, supplementation with probiotics have led to reduced episodes of acute diarrhea by 34 percent and reduced traveler's diarrhea episodes by 8 percent. Probiotic supplementation has also been associated with positive effects in improving lactose intolerance, including reducing symptoms such as bloating, gas, and periodic constipation. Furthermore, probiotics have been studied for use in those with inflammatory bowel diseases, which include a spectrum of disorders characterized by inflammation, ulceration, and abnormal narrowing of the gastrointestinal tract which results in abdominal pain, diarrhea, and gastrointestinal bleeding. The studies have suggested that supplementation with probiotics can offer relief from these symptoms and help maintain remission from symptoms.

With an increased understanding of the importance of the gastrointestinal tract in modulating the immune system, with 70 percent of the immune system residing in the gut, and with the intestinal immune system producing more antibodies than the rest of the body, there has been increased interest in the impact of probiotics on overall gut health and in probiotic-specific impact on the immune system. Part of this suggestion has come from the use of probiotics to restore and rebalance a gut microbiome and to strengthen the microbiome's ability to interact with an immune system. The bacteria can stimulate healthy immune system surveillance and boost the populations of cells that seek out and destroy infecting organisms and cancers. They can also upregulate inflammatory cytokines during the acute stages of an infection, cancer, or other threat to human health and integrity.

One of the more popular probiotics studied for these effects is bifidobacteria, which has long been used as a dietary supplement in Japan. This probiotic bacteria is found in large numbers in breastfeeding children, but as children age, the probiotic bacteria numbers drop as less beneficial and more harmful organisms multiply in the microbiome. Supplementation of bifidobacteria has specifically been related to the suppression of inflammatory cytokine production by the intestines of elderly volunteers, which in turn reduces the burden of inflammation that contributes to risk of cardiovascular disease, cancer, metabolic disease, and early death. Studies with supplementation of bifidobacteria in mice have shown a significant increase in longevity.

Many probiotics have been shown to produce antipathogenic compounds ranging from small molecules to bioactive antimicrobial peptides. The lowering of pH by acids, like lactic and acetic, has bactericidal and bacteriostatic effects. Further, probiotics have been studied for the prevention of infections caused by enteric pathogens. These studies have found a significant reduction in those enteric pathogens, namely S. Typhimurium and C. difficile, compared with control groups. The supplementation of probiotics has also influenced some fermentations parameters which produce organic acids responsible for antipathogenic effects.

Human studies into the use of probiotics to reduce the risk of hypercholesteremia have shown beneficial effects when probiotics are consumed as part of a normal daily diet. Supplementation has been shown to improve protective HDL cholesterol levels in humans and animals with lower total and LDL cholesterol levels, which represents an important reduction in cardiovascular disease risk.

Antigenotoxicity, antimutagenicity, and anti-carcinogenicity are important potential functional properties of probiotics. Several mechanisms are suggested as the cause of these effects and have been investigated in in vitro and animal experiments. These include:

• Inhibition of tumor growth and proliferation of tumor cells by glycopeptides and cytotoxic metabolites of lactobacilli
• Reduction of (pro) carcinogenic, mutagenic, and genotoxic substances, and cancer promoting enzymes in the colon due to modifications of the gut microbiota, decrease in pH, and chemical modification.

Some scientific evidence through studies suggests that probiotics in yogurt, supplement capsules, or vaginal suppositories may help prevent and treat imbalance in the vagina. There is, however, no conclusive evidence showing that probiotics are effective at preventing or treating vaginal conditions, and specifically conditions related to bacterial imbalances in the vaginal microbiome. In a small study performed in 1996, researchers found that women who ate probiotic yogurt had a larger amount of beneficial bacteria in the vaginal microbiome and were less likely to experience conditions related to vaginal imbalance. Furthermore, in a study, women with a vaginal imbalance were given either antibiotics for seven days while others were given the antibiotic with probiotics or placebos. The cure rate at 30 days for those given the antibiotics and probiotics was 90 percent, compared to 40 percent in the antibiotic with placebos group.

Research done into the impact of the intestinal microbiome on allergies has found that children with allergies have lower levels of beneficial bacteria and higher levels of some pathogenic strains. Also, children who later develop allergies show differences in their microbiome composition compared to those who do not. Furthermore, children born by C-section have experienced greater beneficial impacts of probiotics compared to those born through vaginal birth. However, overall there is no conclusive evidence that probiotics can positively effect nasal allergies, food allergies, or asthma. This is despite evidence that pregnant mothers and small children taking probiotics have helped curb children's long-term risk of the allergic skin condition eczema.

Based on accumulated evidence and research into the symbiosis of the gut and lung microbiota environments, there seems to exist bidirectional communication between the gut and lung. The crosstalk is involved in the support of immune homeostasis. It is believed the gastrointestinal inflammation results in lung inflammation through this connection. Dysbiosis, or an imbalance in bacteria, in both gut and lung microbiota is one of the implicated mechanisms in this event. The dysbiosis has been shown to be linked with several respiratory pathological conditions, and shifts in the composition of the lung microbiota toward the gut microbiota have been observed in several respiratory disorders. Such that, the supplementation of probiotics to improve the gut microbiota could, in turn, improve the lung microbiota and overall improve respiratory health.

Due to the observed link between the gut and lung microbiota, and further the high incidence of patients suffering from respiratory diseases to experience gastrointestinal symptoms as well, there is a suggestion that COVID-19 patients, especially those suffering from respiratory symptoms and gastrointestinal symptoms, could benefit from probiotic use. This includes the possibility of probiotic supplementation alleviating symptoms and inflammation.

The benefits of probiotics on gastrointestinal inflammatory diseases, in addition to an increased understanding of the effects of the gastrointestinal microbiome on neurological conditions have led to interest in the potential effectiveness of probiotics in treating or preventing neurological disease. Most of the understanding of the possible positive effects of probiotics on neurological health has focused on the mechanisms of the microbiota-gut-brain axis, which includes encouraging results in studies done on children with autism spectrum disorder.

Many studies have found that the connection between the gut microbiota and the brain, particularly the hypothalamus-pituitary-adrenal axis and autonomic nervous system, is stronger than previously understood. Research has shown that stressful experiences, especially in early life, can interrupt the microbiota profile, restring its multiplicity and richness, and affect the microbial species, including a shift in a microbial component that may promote species of microbiota known to provoke inflammation.

There is an additional relationship between the gut microbiota and its effects on behavior and the brain, involving the vagus nerve. The modulation of the gut microbiota stimulates psychological and behavioral responses with marked dependence on vagal integrity. The gut microbiota have also been shown to influence neuromodulators and neurotransmitters such as GABA, serotonin, monoamines, and brain-derived neurotrophic factors.

Studies done on the effect of probiotics on personality have found no significant differences in personality traits across time points, suggesting the two groups (the experimental group and the control group) remained stable throughout studies. Of course, the dimensions of a personality are complex and consolidated features cannot be easily modified over time. Whether the lack of effect was due to the duration of studies or the dose of probiotics, the suggestion remains that further studies are needed. However, studies into probiotics related to mood and other characteristics, such as sleep, have found different effects.

Studies in non-clinical samples have demonstrated that multi-species probiotics have positive effects on mood. These studies focused on depression and anxiety. Among different indexes of cognitive reactivity to sad mood assessed by means of the LEIDS-R, the scores for acceptance were found to be higher in the experimental group than the control group after six weeks of probiotics intake. Acceptance is an emotion regulatory strategy that facilitates recovery from depression in clinical populations. And, in the study, researchers were able to detect specific changes in positive and negative mood in healthy individuals. The researchers found a reduction in depressive mood state in the group that received probiotics, such that the depression subscale was lower after 6 weeks, suggesting the probiotics were beneficial. The positive effect was maintained after 3 weeks of washout, suggesting a long-term effect.

In the case of state and trait anxiety, no significant differences were found. Further, there were a lack of differences between groups and across points of time during the study. However, the lack of effect on probiotics could be explained by the fact that healthy individuals already have low anxiety scores that cannot be lowered further by probiotics intake.

The gut-brain axis, the bidirectional interaction between the gastrointestinal tract and the nervous system, has seen increased interest as research has linked the gut microflora to a range of health indications. Evidence has suggested partial sleep deprivation may change the microbiota, while jet lag and shift work can also produce dysbiosis, which can in turn promote obesity and glucose intolerance. This evidence is buoyed by studies conducted by researchers at the University of Colorado at Denver, the University of California, San Diego, and Mead Johnson Nutrition reporting that supplementing the diet of lab rats with probiotics improved non-REM sleep in early life and a quicker rebound in REM sleep after stress.

In a study done on the effects of probiotics on cognitive reactivity, mood, and sleep quality, the study did not find a significant difference between the experimental and control groups; however, the experimental group did report improvements in sleep quality after six weeks of probiotics intake. This self-reporting, despite a lack of significant differences in sleep, suggests that probiotics can have a beneficial effect on sleep quality. This includes probiotics being beneficial in patients with chronic fatigue syndrome, chronic pain, and in stressed medical students.

In the case of the stressed medical students, a paper published in Beneficial Microbes reported that daily supplements of a fermented milk product to an experimental group were associated with improved sleep quality for those medical students during their national exams. Another study focused on six weeks of probiotic supplementation in healthy, young women on both physiological well-being (including feelings of depression, anxiety, or cognitive reactivity to sad mood) and quality of sleep. This study concluded that probiotic supplementation was associated with observed improvements in mood, depressive feelings, anger, fatigue, and sleep quality.

Signs of chronic fatigue syndrome (CFS) have been found in the gut bacteria in research conducted at Cornell University, which suggests a further link between the gut and the brain in not only everyday gastrointestinal functions but also in the onset of chronic conditions in which prebiotics such as dietary fibers or probiotics have shown effectiveness. Individuals suffering from CFS have frequently complained of gastrointestinal issues. Through a study of stool samples and microbiome of the gut have found a reduction in anti-inflammatory bacterial species and overall diversity in the gut of CFS patients. This observation has been shared by those with Crohn's disease and ulcerative colitis. The suggestion from these findings is that the activation of pro-inflammatory agents, such as prebiotics, could be important for disease progression in CFS.